microRNA-222 regulates proliferation and apoptosis of fibroblasts in hypertrophic scar via matrix metalloproteinase 1.
- Author:
Yi ZHANG
1
;
Li ZHANG
1
;
Qiyu ZHANG
2
;
Weilong HONG
3
;
Xiaohua LIN
4
Author Information
1. Department of Dermatology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
2. Department of Hepatobiliary Surgery, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
3. Department of Surgical Laboratory, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China.
4. Department of Dermatology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou 325000, China. wzlinxiaohua@163.com.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
genetics;
Cell Proliferation;
genetics;
Cicatrix, Hypertrophic;
Fibroblasts;
Humans;
Matrix Metalloproteinase 1;
metabolism;
MicroRNAs;
metabolism
- From:
Journal of Zhejiang University. Medical sciences
2017;46(6):609-617
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the effect of microRNA(miR)-222 on cell proliferation and apoptosis of fibroblasts in hypertrophic scar (HS) and the underlying mechanisms. Methods: The expression of miR-222 in the HS and the normal skin tissues was detected by real-time RT-PCR. The HS fibroblasts were transfected with miR-222 mimic and miR-222 inhibitor respectively. The cell viability was tested with MTT assay, cell cycle distribution and apoptosis were detected with flow cytometry and the expression levels of proliferation, apoptosis and cell cycle related proteins were determined with Western blot. Direct target of miR-222 was evaluated by dual-luciferase reporter assay. Results: miR-222 was significantly up-regulated in HS tissues compared with normal skin tissues(P<0.05). Overexpression of miR-222 enhanced the cell viability of HS fibroblasts; increased mRNA and protein expressions of proliferating cell nuclear antigen (PCNA), collagen alpha-1 (Ⅰ) chain (Col1A1) and collagen alpha-1 (Ⅲ) chain (Col3A1); increased cell population in S phase and protein expressions of cyclin D1, cyclin E1 and cyclin-dependent kinases 1 (CDK1); inhibited cell apoptosis and reduced protein expressions of caspase-3/9. Overexpression of MMP1 attenuated the effects of miR-222 on the cell viability and apoptosis in fibroblasts, reduced expression levels of PCNA, cyclin D1 and the expression of caspase-3 was increased. Conclusion: miR-222 enhances cell proliferation and inhibits cell apoptosis of HS fibroblasts through negative regulation of MMP1, which suggests that miR-222 and MMP1 might be used as novel biomarkers and targets in diagnostic and therapeutic approaches for HS.
